Courtney I. Jarvis

Therapeutic options for sleep-maintenance and sleep-onset insomnia.

Insomnia, defined as difficulty falling asleep, staying asleep, and/or experiencing restorative sleep with associated impairment or significant distress, is a common condition resulting in significant clinical and economic consequences. Many options are available to treat insomnia, to assist with either falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for articles published between January 1996 and January 2006, evaluated abstracts from recent professional meetings, and contacted the manufacturer of the most recent addition to the pharmacologic armamentarium for insomnia treatment (ramelteon) to gather information. Nonpharmacologic options include stimulus control, sleep hygiene education, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription and over‐the‐counter drug therapies include benzodiazepine and nonbenzodiazepine sedative‐hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and sedating antihistamines. Herbal and alternative preparations include melatonin and valerian. Before recommending any treatment, clinicians should consider patient‐specific criteria such as age, medical history, and other drug use, as well as the underlying cause of the sleep disturbance. All pharmacotherapy should be used with appropriate caution, at minimum effective doses, and for minimum duration of time.

Management Strategies for Premenstrual Syndrome/Premenstrual Dysphoric Disorder

Objective: To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Data Sources: Literature was obtained through searches of MEDLINE Ovid (1950–March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. Study Selection/Data Extraction: All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. Data Synthesis: Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents (or this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. Conclusions: Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on Individual patient symptoms, concomitant medical history, and need for contraception.

Ustekinumab: Treatment of Adult Moderate-to-Severe Chronic Plaque Psoriasis

Objective: To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis. Data Sources: A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets. Study Selection and Data Extraction: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data. Data Synthesis: Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physicians Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8–12 weeks thereafter, based upon response. Conclusions: Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.

Alogliptin A New Dipeptidyl Peptidase-4 Inhibitor for Type 2 Diabetes Mellitus

OBJECTIVE To review the pharmacology, pharmacokinetics, safety, and efficacy of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in the management of type 2 diabetes mellitus (T2DM). DATA SOURCES Searches were conducted in MEDLINE (1946-August 2013) and Embase (1974-August 2013) for English language articles using key words alogliptin, SYR-332, Nesina, Oseni, and Kazano. References of articles were reviewed to identify any additional sources. STUDY SELECTION AND DATA EXTRACTION Articles with adequate sample sizes, evaluating clinically relevant end points were included. DATA SYNTHESIS Alogliptin is a highly selective and potent competitive inhibitor of DPP-4. The DPP-4 enzyme rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. GLP-1, which releases postprandial insulin in response to meals, is thought to be deficient in patients with T2DM. Studies evaluating the role of alogliptin in T2DM have shown significant reductions in blood glucose and hemoglobin A1C (A1C) levels. Alogliptin doses of 12.5 to 25 mg once daily reduced A1C by 0.56% to 0.59% as monotherapy. Patients given alogliptin in addition to other antidiabetic agentsexperienced additional A1C lowering of 0.4% to 0.8%. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections, and headache. Alogliptin demonstrates a neutral effect on weight. A large trial evaluating the cardiovascular safety of alogliptin is currently being conducted. CONCLUSIONS Alogliptin is the fourth DDP-4 inhibitor approved in the US for the treatment of T2DM. It is available alone (Nesina) and in fixed-dose combinations with metformin (Kazano) and pioglitazone (Oseni). It has no demonstrable advantages over other agents in its class.Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor in the management of type 2 diabetes mellitus (T2DM). Data Sources: Searches were conducted in MEDLINE (1946-August 2013) and Embase (1974-August 2013) for English language articles using key words alogliptin, SYR-332, Nesina, Oseni, and Kazano. References of articles were reviewed to identify any additional sources. Study Selection and Data Extraction: Articles with adequate sample sizes, evaluating clinically relevant end points were included. Data Synthesis: Alogliptin is a highly selective and potent competitive inhibitor of DPP-4. The DPP-4 enzyme rapidly inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. GLP-1, which releases postprandial insulin in response to meals, is thought to be deficient in patients with T2DM. Studies evaluating the role of alogliptin in T2DM have shown significant reductions in blood glucose and hemoglobin A1C (A1C) levels. Alogliptin doses of 12.5 to 25 mg once daily reduced A1C by 0.56% to 0.59% as monotherapy. Patients given alogliptin in addition to other antidiabetic agentsexperienced additional A1C lowering of 0.4% to 0.8%. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections, and headache. Alogliptin demonstrates a neutral effect on weight. A large trial evaluating the cardiovascular safety of alogliptin is currently being conducted. Conclusions: Alogliptin is the fourth DDP-4 inhibitor approved in the US for the treatment of T2DM. It is available alone (Nesina) and in fixed-dose combinations with metformin (Kazano) and pioglitazone (Oseni). It has no demonstrable advantages over other agents in its class.

Ulipristal Acetate for Emergency Contraception

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of data of ulipristal acetate, a new emergency contraceptive approved for use up to 120 hours after unprotected intercourse. DATA SOURCES: Articles pertaining to the topic were identified and reviewed through searches of PubMed (1994-March 2011) and clinicaltrials.gov, using the key terms ulipristal and CDB-2914. Ella approval documents were obtained and reviewed from Drugs@FDA on the Food and Drug Administration (FDA) Web site. STUDY SELECTION AND DATA EXTRACTION: All published data and FDA approval documents examining pharmacologic, pharmacokinetic, and clinical studies related to ulipristal acetate as an emergency contraceptive were evaluated. Selected studies included 3 randomized trials and 1 meta-analysis. DATA SYNTHESIS: Ulipristal acetate is a progesterone agonist/antagonist emergency contraceptive approved for the prevention of pregnancy to be taken as soon as possible, within 120 hours after unprotected intercourse or a known or suspected contraceptive failure. Based upon results of the Phase 3 clinical trials used to obtain approval, ulipristal acetate administration was at least as effective as levonorgestrel in the reduction of pregnancy rate when studied alone after unprotected intercourse and when taken up to 120 hours after unprotected intercourse. Commonly reported adverse effects associated with ulipristal acetate in trials included headache, breast tenderness, nausea, and abdominal pain. CONCLUSIONS: Ulipristal acetate is effective as an emergency contraceptive for up to 120 hours after unprotected intercourse. Because ulipristal is available only via prescription, it may be covered by insurance. However, the additional factors of travel expenses and time to make and attend a physician appointment must be taken into account when considering use of ulipristal as an emergency contraceptive. Due to the similarity of its structure to mifepristone, controversy regarding ulipristals mechanism of action has arisen.

Rivaroxaban for Thromboprophylaxis in Patients Undergoing Major Orthopedic Surgery

Objective: To review the pharmacology, pharmacokinetics, and clinical efficacy/safety protile of rivaroxaban to inform health-care professionals of this new agent for the prevention of venous thromboembolism (VTE) in patients undergoing major orthopedic surgery. Data Sources: A literature search was performed in PubMed/MEDLINE (1966–March2010), international Pharmaceutical Abstracts (1970–March 2010), and EMBASE (1990–March 2010), limited to publications in English, using the search terms BAY 59-7939, rivaroxaban, factor Xa inhibitor, hip replacement, and/or knee replacement to identify literature sources. References from retrieved articles were evaluated to identify relevant literature. Unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidance, and advisory committee briefing packets. Study Selection and Data Extraction: All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of rivaroxaban for the prevention of VTE in patients undergoing major orthopedic surgery were included, with preference for clinical data. Data Synthesis: Rivaroxaban use was significantly more effective for thromboprophylaxis in patients undergoing total knee replacement (TKR) or total hip replacement (THR), compared to enoxaparin for the composite incidence of deep vein thrombosis, nonlatal pulmonary embolism, all-cause mortality, and the rate of major VTE; bleeding events occurred at statistically similar rates. In Phase 3 studies, rivaroxaban 10 mg was administered orally 6–8 hours post-surgery and posthemostasis. Thereafter, administration was once daily for 35 days in THR and 10-14daysinTKR. Conclusions: Rivaroxaban has demonstrated comparable safety and superior efficacy to the commonly used low-molecular-weight heparin, enoxaparin. Ongoing and future clinical trials will allow clinicians to further assess the efficacy, safety, and pharmacoeconomics of rivaroxaban.

Bisphosphonates for osteoporosis prevention and treatment

As potent inhibitors of bone resorption, bisphosphonates (BPs) have been used to treat a variety of disorders of calcium and bone metabolism, including osteoporosis. Pagets disease, and metastatic bone disease. Numerous clinical studies have shown BPs to be useful and cost-effective options for the prevention and treatment of fractures and bone loss associated with postmenopausal osteoporosis, senile osteoporosis in men, and glucocorticoid-induced osteoporosis. With proper self-administration in patients without underlying gastrointestinal (GI) disorders, oral bisphosphonates are usually safe, however, they can cause upper GI irritation. The most common side effects are nausea, diarrhea, gastritis, and esophageal irritation Newer, longer-acting BPs and parenteral administration have lead to options for patients who cannot tolerate oral BPs.

State of the Art Reviews: Nonpharmacologic Approaches for the Treatment of Insomnia

Insomnia is a common condition resulting in significant clinical and economic consequences. This review discusses the efficacy of nonpharmacologic treatment options commonly recommended for sleep onset and sleep maintenance insomnia. In addition, the efficacy of these approaches as part of a multifaceted intervention and in comparison to that of pharmacologic options is reviewed. The primary literature and review articles on the nonpharmacologic treatment of insomnia were identified through a MEDLINE search between 1966 and August 2006. Articles on the nonpharmacologic treatment of primary insomnia, including clinical trials on the efficacy of individual and combination treatment options, were reviewed. The nonpharmacologic treatment options for insomnia include stimulus control, sleep hygiene educations, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive-behavioral therapy. These treatment strategies produce significant changes in several sleep parameters of chronic ...